Category Archives: Gilead

Source: Abstract #PS-101 Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6–11 years old with chronic hepatitis C infection—K.F. Murray, et al.

Study Aims and Results: The U.S. Food and Drug Administration (FDA recently expanded the use of Sovaldi (sofosbuvir) and Harvoni (sofosbuvir/ledipasvir) to adolescents 12 years and older who have hepatitis C virus (HCV). However, the only FDA-approved hep C treatment for children under age 12 is peginterferon plus ribavirin, a combination that has many side effects and poor response rates when compared to the new DAAs. This ledipasvir/sofosbuvir +/- ribavirin study enrolled 90 HCV+ children, ages 6–11 years old. The SVR4 rate among the 88 patients who completed the posttreatment Week 4 visit was 99%; one GT1a patient relapsed after 12 weeks.

Conclusion: This all-oral, interferon-free regimen was well tolerated, suggesting its potential as an important treatment option for children 6–11 years old. The study is continuing in children aged 3–5 years old.

Editorial Comments: This study is small and missing the final week 12 data. However, with few options for children, these results seem robust and point towards a hopeful future for children with hepatitis C. It also increases hope for parents; what parent would want to put their child through 24 to 48 weeks of peginterferon rather than 12 weeks of a DAA?

Source: Abstract # THU-248 No impact of RASs on the high efficacy of SOF/VEL/VOX for 12 weeks in DAA-experienced patients: an integrated resistance analysis of the POLARIS-1 and POLARIS-4 studies—C. Sarrazin et al.

Study Aims and Results: The study was a combination of two studies (POLARIS-1 & 4) looking at treating HCV genotype 1 through 6 (pan-genotypic) direct-acting treatment experienced patients with a combination of sofosbuvir, velpatasvir and voxilaprevir.

A total of 445 patients were treated for 12 weeks with the 3-drug combination. Thirty-one percent did not have resistant-associated substitutions (RASs) and the remainder had either one RASs or multiple RASs.

Conclusions: The overall cure rates were 97 to 100% regardless of genotype, cirrhosis/no cirrhosis, type of prior treatment failure or RASs. The 12-week treatment of this combination yields very high cure rates for people who have been previously treated with a direct-acting antiviral medication and who have single or single or double RASs.

Editorial Comments: This is good news for patients and medical providers. The triple combination of sofosbuvir, velpatasvir and voxilaprevir in a once-a-day dose is scheduled to be approved by the Food and Drug Administration (FDA) later this year. It will be a welcome addition to the growing list of HCV medical therapies that are pushing towards 100% cure rates even in people who have not achieved a cure with a prior course of HCV therapy and who have single and double RASs.

Harvoni is approved in the United States for the treatment of genotype 1, 4, 5, or 6 chronic HCV infection in adults and pediatric patients 12 years of age or older or weighing at least 35 kilograms. Harvoni is indicated with ribavirin (RBV) for the treatment of chronic HCV genotype 1 or 4 HCV infection in liver transplant recipients without cirrhosis or with compensated cirrhosis and for genotype 1 HCV-infected patients with decompensated cirrhosis.

Harvoni has a boxed warning in its product label regarding the risk of hepatitis B virus reactivation in HCV/HBV co-infected patients. See below for important safety information.

“Gilead continues to study the safety and efficacy of our medicines in HCV-infected patients with unmet medical need, to help realize the potential for cure,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “In these studies of younger children with hepatitis C and HCV/HBV co-infected patients, Harvoni achieved high cure rates and demonstrated safety consistent with the known profile of the drug.”

Children Aged 6 to 11 Years with Chronic HCV

The estimated prevalence of HCV infection in children is up to 0.4 percent in Europe and the United States and up to 6 percent in resource-limited countries. For children 6-11 years of age weighing less than 35 kilograms, interferon plus RBV for up to 48 weeks remains the standard of care.

Results from an open-label Phase 2 study, led by Karen F. Murray, MD, Professor of Pediatrics at Seattle Children’s Hospital in Seattle, Washington, evaluating an investigational dosage strength of a once-daily single tablet of Harvoni (ledipasvir 45 mg/sofosbuvir 200 mg) in HCV-infected children aged 6 to 11 years, demonstrated cure rates of 99 percent (n=89/90). Genotype 1 patients received 12 weeks of treatment (n=85); one genotype 1 patient who had cirrhosis and prior treatment failure with pegylated interferon plus RBV received 24 weeks of treatment; genotype 3 patients (n=2) received Harvoni plus RBV for 24 weeks; genotype 4 patients (n=2) received Harvoni for 12 weeks. One treatment-naïve genotype 1 patient relapsed; all other patients achieved SVR12, the primary efficacy endpoint. The most common adverse events (>10 percent) all of which were mild to moderate in severity, were abdominal pain, headache, diarrhea, vomiting, nausea, fatigue, pyrexia, cough and oropharyngeal pain. No patients discontinued therapy.

HCV/HBV Co-infected Patients

The global prevalence of HCV/HBV co-infection is estimated to be 1.7–3.9 million. Reactivation of HBV infection during treatment of HCV infection with direct-acting antiviral agents has been reported in the postmarketing setting. However, clinical trials to more systematically assess the safety and efficacy of direct-acting antiviral therapy in HCV/HBV co-infected patients with active HBV infection have not been conducted.

Three patients had serious adverse events that were not considered to be drug-related, including optic neuritis, post-procedural bleeding and duodenal ulcer bleeding. The most common adverse events reported (≥5 percent of patients) were headache, upper respiratory infection and fatigue.

Of the 111 patients enrolled, 23 (21 percent) experienced an increase in HBV DNA of at least 2 log10 IU/mL during or following Harvoni treatment. However, no patient experienced a grade 3 or 4 ALT increase or any clinical manifestations suggestive of HBV reactivation. There were two patients that started HBV treatment based on increases in HBV DNA and mild elevations in ALT without symptoms.

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Harvoni.

HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death.Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents.

If Harvoni is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.

Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

In addition to rifampin and St. John’s wort, coadministration of Harvoni is also not recommended with carbamazepine,oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.

Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that physicians may not see the benefits of prescribing Harvoni in special patient populations with HCV infection. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2016, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full prescribing information for Harvoni, including BOXED WARNING, is available at www.gilead.com.

Harvoni is a registered trademark of Gilead Sciences, Inc., or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

– SOF/VEL/VOX Granted an Accelerated Assessment by the European Medicines Agency –

FOSTER CITY, Calif.–(BUSINESS WIRE)–Jan. 20, 2017– Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the company’s Marketing Authorization Application (MAA) for the investigational, once-daily, single tablet regimen of sofosbuvir 400 mg, velpatasvir 100 mg and voxilaprevir 100 mg (SOF/VEL/VOX) for the treatment of chronic hepatitis C virus (HCV)-infected patients has been fully validated and is now under assessment by the European Medicines Agency (EMA).

“Direct-acting antiviral treatments have transformed our ability to treat hepatitis C; however, for some patients who have failed to achieve a cure with these regimens, effective and well-tolerated therapies are still needed,” said Norbert Bischofberger, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “The submission of this application reflects our continued commitment to provide treatment options for this life-threatening disease to as many patients as possible, including those who have failed previous direct-acting antiviral therapy, in Europe and around the world.”

The MAA for SOF/VEL/VOX is supported by data from two Phase 3 studies (POLARIS-1 and POLARIS-4), which evaluated 12 weeks of the fixed-dose combination in direct-acting antiviral (DAA)-experienced patients with hepatitis C genotypes 1-6, including those who failed prior treatment with an NS5A inhibitor-containing regimen. Across the two studies, 97 percent of patients treated with SOF/VEL/VOX (n=430/445) achieved the primary efficacy endpoint of SVR12. The MAA also includes data from two additional phase 3 studies (POLARIS-2 and POLARIS-3), which evaluated 8 weeks of SOF/VEL/VOX in 611 DAA-naïve patients with genotypes 1-6. In POLARIS-3, 96 percent of patients with genotype 3 infection and cirrhosis treated with SOF/VEL/VOX (n=106/110) achieved the primary efficacy endpoint of SVR12. The most common adverse events among patients who received SOF/VEL/VOX were headache, fatigue, diarrhea and nausea.

SOF/VEL/VOX for the treatment of HCV will be reviewed by the EMA under the centralized licensing procedure for all 28 member states of the European Union, Norway and Iceland. The review will follow an accelerated procedure reserved for medicinal products expected to be of major public health interest. Gilead also submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for SOF/VEL/VOX on December 8, 2016.

SOF/VEL/VOX is an investigational product and its safety and efficacy has not been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that the European Commission or other regulatory agencies, including the FDA, may not approve SOF/VEL/VOX for the treatment of chronic hepatitis C and that any marketing approvals, if granted, may have significant limitations on its use. As a result, Gilead may not be able to successfully commercialize SOF/VEL/VOX for chronic hepatitis C. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10­Q for the quarter ended September 30, 2016, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Two drug combinations from Gilead and AbbVie that could improve treatment of chronic hepatitis C have been granted accelerated review in the EU.

Gilead’s application is for a three drug combination of NS5B polymerase inhibitor sofosbuvir, NS5A inhibitor velpatasvir and pan-genotypic protease inhibitor voxilaprevir – given over 12 weeks – that could achieve a cure for chronichepatitis C virus(HCV) patients who have failed other regimens.

The new directly-acting antivirals can now cure more than 90% of people with all hepatitis C virus (HCV) genotypes, but there is still room for better options for the most difficult-to-treat people.

Source: Abstract #PS-101 Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6–11 years old with chronic hepatitis C infection—K.F. Murray, et al.

Study Aims and Results: The U.S. Food and Drug Administration (FDA recently expanded the use of Sovaldi (sofosbuvir) and Harvoni (sofosbuvir/ledipasvir) to adolescents 12 years and older who have hepatitis C virus (HCV). However, the only FDA-approved hep C treatment for children under age 12 is peginterferon plus ribavirin, a combination that has many side effects and poor response rates when compared to the new DAAs. This ledipasvir/sofosbuvir +/- ribavirin study enrolled 90 HCV+ children, ages 6–11 years old. The SVR4 rate among the 88 patients who completed the posttreatment Week 4 visit was 99%; one GT1a patient relapsed after 12 weeks.

Conclusion: This all-oral, interferon-free regimen was well tolerated, suggesting its potential as an important treatment option for children 6–11 years old. The study is continuing in children aged 3–5 years old.

Editorial Comments: A meta-analysis review of acute HCV in people with HIV would be helpful. This will narrow down the optimal timeframe to treat. Still, the cure rates are very encouraging! This study is small and missing the final week 12 data. However, with few options for children, these results seem robust and point towards a hopeful future for children with hepatitis C. It also increases hope for parents; what parent would want to put their child through 24 to 48 weeks of peginterferon rather than 12 weeks of a DAA?